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- EMDB-44246: Cryo-EM structure of HIV-1 JRFL v6 Env in complex with vaccine-el... -

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Basic information

Entry
Database: EMDB / ID: EMD-44246
TitleCryo-EM structure of HIV-1 JRFL v6 Env in complex with vaccine-elicited, Membrane Proximal External Region (MPER) directed antibody DH1317.4.
Map dataHalf Map B
Sample
  • Complex: Complex of JRFL.SOSIP.v6 with DH1317.4, VRC01 and PGT145
    • Protein or peptide: JRFL.SOSIP.v6
    • Protein or peptide: DH1317.4 Light Chain
    • Protein or peptide: DH1317.4 Heavy Chain
KeywordsMembrane Proximal External Region / Vaccine-elicited antibody / DH1317.4 / JRFL SOSIP / VIRAL PROTEIN
Biological speciesHomo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 6.7 Å
AuthorsAcharya P / Parsons R / Janowska K / Williams WB / Alam M / Haynes BF
Funding support United States, 1 items
OrganizationGrant numberCountry
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)U54 AI170752 United States
CitationJournal: Cell / Year: 2024
Title: Vaccine induction of heterologous HIV-1-neutralizing antibody B cell lineages in humans.
Authors: Wilton B Williams / S Munir Alam / Gilad Ofek / Nathaniel Erdmann / David C Montefiori / Michael S Seaman / Kshitij Wagh / Bette Korber / Robert J Edwards / Katayoun Mansouri / Amanda Eaton ...Authors: Wilton B Williams / S Munir Alam / Gilad Ofek / Nathaniel Erdmann / David C Montefiori / Michael S Seaman / Kshitij Wagh / Bette Korber / Robert J Edwards / Katayoun Mansouri / Amanda Eaton / Derek W Cain / Mitchell Martin / JongIn Hwang / Aria Arus-Altuz / Xiaozhi Lu / Fangping Cai / Nolan Jamieson / Robert Parks / Maggie Barr / Andrew Foulger / Kara Anasti / Parth Patel / Salam Sammour / Ruth J Parsons / Xiao Huang / Jared Lindenberger / Susan Fetics / Katarzyna Janowska / Aurelie Niyongabo / Benjamin M Janus / Anagh Astavans / Christopher B Fox / Ipsita Mohanty / Tyler Evangelous / Yue Chen / Madison Berry / Helene Kirshner / Elizabeth Van Itallie / Kevin O Saunders / Kevin Wiehe / Kristen W Cohen / M Juliana McElrath / Lawrence Corey / Priyamvada Acharya / Stephen R Walsh / Lindsey R Baden / Barton F Haynes /
Abstract: A critical roadblock to HIV vaccine development is the inability to induce B cell lineages of broadly neutralizing antibodies (bnAbs) in humans. In people living with HIV-1, bnAbs take years to ...A critical roadblock to HIV vaccine development is the inability to induce B cell lineages of broadly neutralizing antibodies (bnAbs) in humans. In people living with HIV-1, bnAbs take years to develop. The HVTN 133 clinical trial studied a peptide/liposome immunogen targeting B cell lineages of HIV-1 envelope (Env) membrane-proximal external region (MPER) bnAbs (NCT03934541). Here, we report MPER peptide-liposome induction of polyclonal HIV-1 B cell lineages of mature bnAbs and their precursors, the most potent of which neutralized 15% of global tier 2 HIV-1 strains and 35% of clade B strains with lineage initiation after the second immunization. Neutralization was enhanced by vaccine selection of improbable mutations that increased antibody binding to gp41 and lipids. This study demonstrates proof of concept for rapid vaccine induction of human B cell lineages with heterologous neutralizing activity and selection of antibody improbable mutations and outlines a path for successful HIV-1 vaccine development.
History
DepositionMar 23, 2024-
Header (metadata) releaseAug 14, 2024-
Map releaseAug 14, 2024-
UpdateAug 14, 2024-
Current statusAug 14, 2024Processing site: RCSB / Status: Released

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Structure visualization

Supplemental images

emd_44246.png

Downloads & links

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Map

FileDownload / File: emd_44246.map.gz / Format: CCP4 / Size: 282.6 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
AnnotationHalf Map B
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
1.08 Å/pix.
x 420 pix.
= 453.6 Å		1.08 Å/pix.
x 420 pix.
= 453.6 Å		1.08 Å/pix.
x 420 pix.
= 453.6 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 1.08 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.85
Minimum - Maximum-0.74990815 - 3.5399256
Average (Standard dev.)0.005242441 (±0.13107738)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions420420420
Spacing420420420
CellA=B=C: 453.6 Å
α=β=γ: 90.0 °

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Supplemental data

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Half map: Main sharpened map from cryosparc.

Fileemd_44246_half_map_1.map
AnnotationMain sharpened map from cryosparc.
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Half map: Half Map A

Fileemd_44246_half_map_2.map
AnnotationHalf Map A
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Sample components

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Entire : Complex of JRFL.SOSIP.v6 with DH1317.4, VRC01 and PGT145

EntireName: Complex of JRFL.SOSIP.v6 with DH1317.4, VRC01 and PGT145
Components
  • Complex: Complex of JRFL.SOSIP.v6 with DH1317.4, VRC01 and PGT145
    • Protein or peptide: JRFL.SOSIP.v6
    • Protein or peptide: DH1317.4 Light Chain
    • Protein or peptide: DH1317.4 Heavy Chain

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Supramolecule #1: Complex of JRFL.SOSIP.v6 with DH1317.4, VRC01 and PGT145

SupramoleculeName: Complex of JRFL.SOSIP.v6 with DH1317.4, VRC01 and PGT145
type: complex / ID: 1 / Parent: 0 / Macromolecule list: all
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 450 MDa

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Macromolecule #1: JRFL.SOSIP.v6

MacromoleculeName: JRFL.SOSIP.v6 / type: protein_or_peptide / ID: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
SequenceString: MPMGSLQPLA TLYLLGMLVA SCLGVEKLWV TVYYGVPVWK EACTTLFCAS DAKAYDTKVR NVWATHCCVP TDPNPQEVVL ENVTEHFNMW KNNMVEQMQE DIISLWDQSL KPCVKLTPLC VTLNCKDVNA TNTTNDSEGT MERGEIKNCS FNITTSIRDK VQKEYALFYK ...String:
MPMGSLQPLA TLYLLGMLVA SCLGVEKLWV TVYYGVPVWK EACTTLFCAS DAKAYDTKVR NVWATHCCVP TDPNPQEVVL ENVTEHFNMW KNNMVEQMQE DIISLWDQSL KPCVKLTPLC VTLNCKDVNA TNTTNDSEGT MERGEIKNCS FNITTSIRDK VQKEYALFYK LDVVPIDNNN TSYRLISCDT SVITQACPKI SFEPIPIHYC APAGFAILKC NDKTFNGKGP CKNVSTVQCT HGIRPVVSTQ LLLNGSLAEE EVVIRSDNFT NNAKTIIVQL KESVEINCTR PNNNTRKSIH IGPGRWFYTT GEIIGDIRQA HCNISRAKWN DTLKQIVIKL REQFENKTIV FNHSSGGDPE IVMHSFNCGG EFFYCNSTQL FNSTWNNNTE GSNNTEGNTI TLPCRIKQII NMWQEIGKAM YAPPIRGQIR CSSNITGLLL TRDGGINENG TEIFRPGGGD MRDNWRSELY KYKVVKIEPL GVAPTKCKRR VVGRRRRRRA VGIGAVFLGF LGAAGSTMGA ASMTLTVQAR QLLSGIVQQQ NNCLRAPECQ QRMLQLTVWG IKQLQARVLA VERYLGDQQL LGIWGCSGKL ICCTAVPWNA SWSNKSLDRI WNNMTWMEWE REIDNYTSEI YTLIEESQNQ QEKNEQELLE LDKWASLWNW FDITKWLWYI KIFIMIVGGL VGLRLVFTVL SIVNRVRQGY SPLSFQTLLP APRGPDRPEG IEEEGGERDR DRSGRLVNGF LALIWVDLRS LCLFSYHRLR DLLLTVTRIV ELLGRRGWEV LKYWWNLLQY WSQELKNSAV SLLNATAIAV AEGTDRIIEA LQRTYRAILH IPTRIRQGLE RALL

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Macromolecule #2: DH1317.4 Light Chain

MacromoleculeName: DH1317.4 Light Chain / type: protein_or_peptide / ID: 2 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: MGWSCIILFL VATATGVHSD IQMTQSPSSL SASVGDRVTI TCRASQVISS WVAWYQQKPG QAPKLLIFGT SSLQNGVPSR FSGSGSGTYF TLTISSLQPE DFATYYCQQA NSFPPKWPFG QGTKVEIKRT VAAPSVFIFP PSDEQLKSGT ASVVCLLNNF YPREAKVQWK ...String:
MGWSCIILFL VATATGVHSD IQMTQSPSSL SASVGDRVTI TCRASQVISS WVAWYQQKPG QAPKLLIFGT SSLQNGVPSR FSGSGSGTYF TLTISSLQPE DFATYYCQQA NSFPPKWPFG QGTKVEIKRT VAAPSVFIFP PSDEQLKSGT ASVVCLLNNF YPREAKVQWK VDNALQSGNS QESVTEQDSK DSTYSLSSTL TLSKADYEKH KVYACEVTHQ GLSSPVTKSF NRGEC

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Macromolecule #3: DH1317.4 Heavy Chain

MacromoleculeName: DH1317.4 Heavy Chain / type: protein_or_peptide / ID: 3 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: MGWSCIILFL VATATGVHSQ VQLVQSGSEL RKPGASVKVS CKASGYTFTS YAINWVRQAP GQGLEWMGWI NTNTGIPTSA QALTGRFVFS VDSSVNTAYL QISSLKAEDT AVYYCARVRR GGYNNYYMDV WGTGTTVTVS SASTKGPSVF PLAPSSKSTS GGTAALGCLV ...String:
MGWSCIILFL VATATGVHSQ VQLVQSGSEL RKPGASVKVS CKASGYTFTS YAINWVRQAP GQGLEWMGWI NTNTGIPTSA QALTGRFVFS VDSSVNTAYL QISSLKAEDT AVYYCARVRR GGYNNYYMDV WGTGTTVTVS SASTKGPSVF PLAPSSKSTS GGTAALGCLV KDYFPEPVTV SWNSGALTSG VHTFPAVLQS SGLYSLSSVV TVPSSSLGTQ TYICNVNHKP SNTKVDKKVE P

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Experimental details

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Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

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Sample preparation

BufferpH: 7.2
VitrificationCryogen name: ETHANE

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Electron microscopy

MicroscopeTFS KRIOS
Image recordingFilm or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 64.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.4 µm / Nominal defocus min: 0.8 µm
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

Startup modelType of model: NONE
Final reconstructionApplied symmetry - Point group: C1 (asymmetric) / Resolution.type: BY AUTHOR / Resolution: 6.7 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC (ver. 4.4.1) / Number images used: 120899
Initial angle assignmentType: MAXIMUM LIKELIHOOD / Software - Name: cryoSPARC (ver. 4.4.1)
Final angle assignmentType: MAXIMUM LIKELIHOOD / Software - Name: cryoSPARC (ver. 4.4.1)
Final 3D classificationNumber classes: 3 / Software - Name: cryoSPARC (ver. 4.4.1)
FSC plot (resolution estimation)

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